Social stress linked to disease of aging and shortened lifespan

Society is becoming older and more vulnerable to chronic diseases that result in a poor quality of life. Life stress, which before being a scientific notion is instinctively clear to most due to its universality, is an important risk factor promoting the vulnerability to disease. So far, there is limited understanding of the biology of this phenomenon that can help the development of therapeutic solutions.

A study from University of Minnesota Medical School researchers, published in the journal Aging Cell, has demonstrated that psychosocial stress can shorten the lifespan in an animal model. For years, stress and low socio-economic status has been connected to morbidity and mortality in humans, but until now, it has not been mechanically understood or explored in animal models.

Figure legend. A. Survival curve comparing low social status mice (Sub = Subordinate) to high social status mice (Dom = Dominant), showing a significant shorter survival for Sub mice. B. markers of atherosclerosis in the aortic valve of low social status mice, with red arrows indicating regions of calcification (1), immune cell infiltration with Mac-2 staining (2), rupture and immune cell infiltration (3), and red Alzarin staining for calcification (4). C. levels of p16 and p53 protein expression, that increases in aging cells, in tissues from low and high social status mice, showing when quantified as well as visually from a Western blot gel, the increased amount in tissue of Subordinate mice origin.

The research team developed an animal model based on social hierarchy between male mice established through aggressive behavior over their lifetime and then were able to characterize mouse healthspan, biological markers of so-called senescent (aging) cells that accumulate with aging, and lifespan for animals of both high and low social status.

The study demonstrates a link between the shorter lifespan of low social status individuals with a poorer health span, the development of atherosclerosis and cellular senescence. Atherosclerosis – essentially the narrowing and clogging of arteries due to fatty deposits – is one of the leading causes of cardiovascular disease in the elderly which is projected to affect more than 40 percent of Americans by 2030. Senescent cells accumulate during aging and are now being linked to debilitating diseases, such as cardiovascular, muscular and neurological disease.

“Paradoxically, the negative impact of chronic stress and low socioeconomic status on human health is a very well described phenomenon,” said Alessandro Bartolomucci, Ph.D., associate professor in the Medical School and senior author of the study. “However, since this has never been replicated in any preclinical model, the mechanism of the association between stress, aging and survival remains unclear. That’s where our study comes in.”

The research team now hopes to use this study and future studies to better understand the mechanisms of stress-induced diseases and the extent to which cellular senescence drives shortened lifespan, cardiovascular and neurodegenerative diseases. Ultimately, the goal would be the development of efficacious therapies based both on psychological stress management and senotherapeutic treatments.